Our long term goal is to develop methods for automated, high-throughput DNA analysis for genetic typing of disease markers. We propose to develop an integrated instrument system and procedures to perform simple sequence repeat sizing of fluorescent PCR figments by capillary array electrophoresis. During Phase II we propose to: 1) Test and Optimize the integrated 4-color CAE system using protocols developed in Phase I for linkage analysis; 2) Enhance genotyping software by evaluating sizing algorithms and by integrating genotyping and pedigree editing tools; 3) Optimize mutation screening methods using known normal and disease-related alleles. The CAE system performance will then be validated in a molecular genetics testing laboratory. The studies in this proposal will demonstrate the utility and applicability of CAE to a broad range of genetic typing applications. The integrated methods, instrument, and software will have the capacity to analyze up to 9.1 million genotypes per year, increasing throughput by a factor of 5-7 over current systems. Availability of this high-throughput system will significantly enhance the application of genetic typing in the health sciences. PROPOSED COMMERCIAL APPLICATION: A capillary array genetic analysis system has significant potential to improve the U.S. economic growth by accelerating the rate that new genetic information is generated. Reliable, cost-efficient genetic typing will have significant impact on healthcare, agribusiness, forensic analysis, and pharmaceutical industry sectors. The systems offer the potential to significantly control healthcare costs through economical yet accurate early diagnosis leading to prevention or effective treatment of serious genetic disorders, including neurodegenerative and neuropsychiatric illnesses.